N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin

Abstract

The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4 nm for uncoated liposomes and 657.7 nm for TMC-coated liposomes), and zeta potential (–9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C_max = 46.13 μg/L, t_1/2 = 12.05 hours, AUC = 416.58 μg/L·h), compared with CUR encapsulated by uncoated liposomes (C_max = 32.12 μg/L, t_1/2 = 9.79 hours, AUC = 263.77 μg/L·h) and CUR suspension (C_max = 35.46 μg/L, t_1/2 = 3.85 hours, AUC = 244.77 μg/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR.

Keywords::

• Curcumin
• N-trimethyl chitosan chloride
• liposomes
• oral delivery